This research aims to identify the changes in the genetic material or its regulation which must occur for mammalian cells to undergo neoplastic progression in response to tumor promoters. Results suggest that promotability behaves as a dominant trait. Transfection of whole cell DNA from promotion-sensitive (P+) cells into promotion-resistant (P-) cells results in transfer of promotion sensitivity. Transfection of DNA from nonpromotable cells yields a response to TPA that is no higher than the untransfected background. Transfected promotability is stable. The restriction enzyme sensitivity (resistance to BglII) and size class (around 10 Kb) of the P+ gene has been characterized. Epidermal tumor cell DNA can be expressed in P+ but not in P- cells suggesting a permissive genotype for the former. Current efforts are directed to cloning the P+ gene, with an ultimate objective of isolating and elucidating the function of the P+ gene product. The basis for resistance of P- cells will be investigated as will the relationship of P+ genes to transforming genes. It is expected that P+ genes specify an event involved in induction of malignancy, which may not be involved in maintenance of the malignant phenotype.